Testosterone can also be converted into a potent nonaromatizable androgen, 5αα-dihydrotestosterone (DHT), by the enzyme 5α-reductase (see
Fig. 44.8 ). There are two isoforms of 5α-reductase, type 1 and type 2. Major sites of 5α-reductase 2 expression are the male urogenital tract, genital skin, hair follicles, and liver. 5α-Reductase 2 generates DHT, which is required for masculinization of the external genitalia in utero and for many of the changes associated with puberty, including growth and activity of the prostate gland (see ), growth of the penis, darkening and folding of the scrotum, growth of pubic and axillary hair, growth of facial and body hair, and increased muscle mass (
Fig. 44.9 ). The onset of 5α-reductase 1 expression occurs at puberty. This isozyme is expressed primarily in the skin and contributes to sebaceous gland activity and the acne associated with puberty. Because DHT has strong growth-promoting (i.e., trophic) effects on its target organs, development of selective 5α-reductase 2 inhibitors has benefited the treatment of prostatic hypertrophy and prostatic cancer.
Testosterone has a direct action (i.e., without conversion to DHT) in several cell types (see
Fig. 44.9).
As mentioned earlier, testosterone regulates Sertoli cell function. It induces development of the male tract from the mesonephric duct in the absence of 5α-reductase. Testosterone has several metabolic effects, including increasing very low-density lipoprotein (VLDL) and LDL while decreasing HDL, promoting deposition of abdominal adipose tissue, increasing red blood cell production, promoting bone growth and health, and exerting a protein anabolic effect on muscle. Testosterone is sufficient to maintain erectile function and libido.
Mechanism of Androgen Action
Testosterone and DHT act through the same androgen receptor (AR). The AR resides in the cytoplasm bound to chaperone proteins in the absence of ligand.Testosterone-AR